We are studying new approaches to nucleotide sequencing. Our primary interest is in those eukaryotic nucleic acid sequences, including mRNA sequences, which were very difficult to determine using existing RNA sequencing techniques. At present our efforts are focused on the use of ribosubstitution sequencing methods and on the use of reverse transcriptase as a sequencing tool. Both of these approaches have been very successful and we are also working on some other newer methods which we think will be especially effective when used in combination with the existing approaches.